Neuronal nitric oxide synthase (nNOS) mRNA is down-regulated, and constitutive NOS enzymatic activity decreased, in thoracic dorsal root ganglia and spinal cord of the rat by a substance P N-terminal metabolite.
Neuronal nitric oxide synthase (nNOS) mRNA is down-regulated, and constitutive NOS enzymatic activity decreased, in thoracic dorsal root ganglia and spinal cord of the rat by a substance P N-terminal metabolite.
复制标题
P N 末端代谢物可下调大鼠胸背根神经节和脊髓中的神经元一氧化氮合酶 (nNOS) mRNA，并且组成型 NOS 酶活性降低。
DOI：
10.1046/j.0953-816x.2001.01675.x
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Larson,AA
中科院分区：
文献类型：
--
作者：
Kovacs,KJ;Cai,Y;Larson,AA
Nitric oxide (NO) in the spinal cord plays a role in sensory and autonomic activity. Pain induced by acetic acid in the abdominal stretch (writhing) assay and hyperalgesia associated with chronic pain are highly sensitive to NO synthase (NOS) inhibitors. Because substance P (SP) is released and up‐regulated in some models of chronic pain, we hypothesized that an accumulation of SP metabolites may influence NOS expression and activity. To test this hypothesis, we examined the effect of intrathecally (i.t.) injected substance P (1‐7) [SP(1‐7)], the major metabolite of SP in the rat, on neuronal NOS (nNOS) mRNA in the thoracic and lumbar spinal cord, dorsal root ganglia (DRG) and on the corresponding constitutive NOS (cNOS) enzyme activity. Detected using quantitative RT‐PCR, nNOS mRNA content in the thoracic spinal cord was decreased 6 h after injection of 5 µmol of SP(1‐7) and returned to control 2 days later. In thoracic DRG, nNOS mRNA was reduced 48 h after SP(1‐7). The cNOS enzymatic activity in thoracic spinal tissue was gradually decreased to a minimum at 72 h. Down‐regulation of NOS by SP(1‐7) in the thoracic area appears to be highly associated with capsaicin‐sensitive primary afferent neurons. No similar changes in either parameter were measured in the lumbar area after SP(1‐7). These data suggest that N‐terminal SP fragments, which are known to cause long‐term antinociception in the writhing assay, may do so by their ability to down‐regulate NO synthesis along nociceptive pathways.
